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GSE51021
Homo sapiens
25 Downloadable Samples
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Lymph node metastasis is a poor prognosis indicator in esophageal cancer. Although tumor spreading currently forms the main basis for therapy selection, the molecular mechanisms underlying the metastatic pathway remain insufficiently understood. Several studies aimed to investigate these mechanisms but focused mainly on regulatory patterns in the tumors themselves and/or the invaded lymph nodes. To date no study has yet investigated the potential changes on transcription level, which take place within the yet non-invaded niche. Here we provide a comprehensive description of these regulations in patients. In this study the transcriptomic profiles of regional lymph nodes were determined for two patient groups: patients classified as pN1 (metastasis) or pN0 (no metastasis) respectively. All investigated lymph nodes, also those from pN1 patients, were still free of metastasis. The gene expression data was obtained via microarray analysis. Top candidates were validated via PCR and immunohistochemistry. The results show that regional lymph nodes of pN1 patients differ decisively from those of pN0 patients even before metastasis has taken place. In the pN0 group distinct immune response patterns were observed. In contrast, lymph nodes of the pN1 group exhibited a clear profile of reduced immune response and reduced proliferation, but increased apoptosis, enhanced hypoplasia and morphological conversion processes. DKK1 was the most significant gene associated with the molecular mechanisms taking place in lymph nodes of patients suffering from metastasis (pN1). We assume that the two molecular profiles observed constitute two different stages of a progressive disease. Finally we suggest that DKK1 might play an important role within the mechanisms leading to lymph node metastasis.
Publication Title
Molecular changes in pre-metastatic lymph nodes of esophageal cancer patients.
Sample Metadata Fields
Specimen part, Subject
View Samples- Mus musculus
- 34 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Low-grade and high-grade mammary carcinomas in WAP-T transgenic mice are independent entities distinguished by Met expression.
Sample Metadata Fields
Specimen part, Disease stage, Time
View Samples- Mus musculus
- 28 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Transgenic expression in mice of two synergistically acting SV40 early region encoded proteins, large (LT) and small (sT) tumor antigens, in the mammary epithelium recapitulates loss of p53 and Rb function and deregulation of PP2A-controlled mitogenic pathways in human breast cancer. In primiparous mice, WAP-promoter driven expression of SV40 proteins induces well and poorly differentiated mammary adenocarcinomas. We performed a correlative aCGH and gene expression analysis of 25 monofocal tumors, representing four histopathological grades, to explore the molecular traits of SV40-induced mammary tumors and to emphasize the relevance of this tumor model for human breast tumorigenesis.
Publication Title
Low-grade and high-grade mammary carcinomas in WAP-T transgenic mice are independent entities distinguished by Met expression.
Sample Metadata Fields
Specimen part, Disease stage
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Transgenic expression in mice of two synergistically acting SV40 early region encoded proteins, large (LT) and small (sT) tumor antigens, in the mammary epithelium recapitulates loss of p53 and Rb function and deregulation of PP2A-controlled mitogenic pathways in human breast cancer. In primiparous mice, WAP-promoter driven expression of SV40 proteins induces well and poorly differentiated mammary adenocarcinomas. We performed a correlative aCGH and gene expression analysis of 25 monofocal tumors, representing four histopathological grades, to explore the molecular traits of SV40-induced mammary tumors and to emphasize the relevance of this tumor model for human breast tumorigenesis.
Publication Title
Low-grade and high-grade mammary carcinomas in WAP-T transgenic mice are independent entities distinguished by Met expression.
Sample Metadata Fields
Specimen part, Time
View Samples- Mus musculus
- 10 Downloadable Samples
- Affymetrix Mouse Genome 430A 2.0 Array (mouse430a2)
Description
Precise nucleosome-positioning patterns at promoters are thought to be crucial for faithful transcriptional regulation. However, the mechanisms by which these patterns are established and dynamically maintained and subsequently contribute to transcriptional control are poorly understood. The Swi/Snf (Baf) chromatin remodeling complex is a master developmental regulator and tumor suppressor that is capable of mobilizing nucleosomes in biochemical assays. Yet, its role in establishing the nucleosome landscape in vivo is unclear. Here we have inactivated Snf5 and Brg1, core subunits of the mammalian Swi/Snf complex, to evaluate their effects on chromatin structure and transcription levels genome-wide. We find that inactivation of either subunit leads to disruptions of specific nucleosome patterning combined with a loss of overall nucleosome occupancy at a large number of promoters, regardless of their association with CpG islands. These rearrangements are accompanied by gene expression changes that promote cell proliferation. Collectively, these findings define a direct relationship between chromatin-remodeling complexes, chromatin structure, and transcriptional regulation.
Publication Title
Swi/Snf chromatin remodeling/tumor suppressor complex establishes nucleosome occupancy at target promoters.
Sample Metadata Fields
Specimen part
View Samples- Danio rerio
- 4 Downloadable Samples
IlluminaHiSeq4000
Description
We report high-throughput profiling of gene expression from whole zebrafish ventricles. We profile mRNA in uninjured ventricles and those undergoing regeneration 14 days after genetic ablation. This study provides a framework for understanding transcriptional changes during adult models of regeneration. Overall design: Examination of gene expression in cardiomyocytes under different states of proliferation.
Publication Title
Resolving Heart Regeneration by Replacement Histone Profiling.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 8 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
It is unclear how nanosecond electrical pulses affect gene expression.
Publication Title
Evaluation of the Genetic Response of U937 and Jurkat Cells to 10-Nanosecond Electrical Pulses (nsEP).
Sample Metadata Fields
Specimen part, Cell line
View Samples- Homo sapiens
- 7 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
It is unclear how nanosecond electrical pulses affect gene expression.
Publication Title
Evaluation of the Genetic Response of U937 and Jurkat Cells to 10-Nanosecond Electrical Pulses (nsEP).
Sample Metadata Fields
Specimen part, Cell line
View Samples- Drosophila melanogaster
- 4 Downloadable Samples
- Illumina HiSeq 2000
Description
mRNA expression levels were determined by NGS for wildtype larvae as well as for larvae lacking HP1a [Su(var)205^04/Su(var)205^05 transheterozygotes]. Overall design: RNA samples from wildtype (OR) and HP1a mutant third instar larvae were examined, using duplicate biological samples and Illumina NGS.
Publication Title
Enrichment of HP1a on Drosophila chromosome 4 genes creates an alternate chromatin structure critical for regulation in this heterochromatic domain.
Sample Metadata Fields
Subject
View Samples- Homo sapiens
- 34 Downloadable Samples
- IlluminaHiSeq2000
Description
SMARCB1 (SNF5/INI1/BAF47), a core subunit of the SWI/SNF (BAF) chromatin remodeling complex, is inactivated in nearly all pediatric rhabdoid tumors. These aggressive cancers are among the most genomically stable, suggesting an epigenetic mechanism by which SMARCB1 loss drives transformation. Here, we show that despite indistinguishable mutational landscapes, human RTs show distinct enhancer H3K27ac signatures, which reveal remnants of differentiation programs. We show that SMARCB1 is required for the integrity of SWI/SNF complexes and that its loss alters enhancer targeting markedly impairing SWI/SNF binding to typical enhancers, particularly those required for differentiation, while maintaining SWI/SNF binding at super-enhancers. We show that these retained super-enhancers are essential for rhabdoid tumor survival, including some that are shared across all subtypes, such as SPRY1, and other lineage-specific super-enhancers like SOX2 in brain-derived RTs. Taken together, our findings reveal a novel chromatin-based epigenetic mechanism underlying the tumor suppressive activity of SMARCB1. Overall design: RNA-seq in six Smarcb1 deficient rhabdoid tumor cell lines, before and after Smarcb1 re-expression.
Publication Title
SMARCB1-mediated SWI/SNF complex function is essential for enhancer regulation.
Sample Metadata Fields
No sample metadata fields
View Samples